This Working Group studies the high-resolution structure and function of proteins and other macromolecules using x-ray diffraction methods. Although the groups' research interests are broadly based in all aspects of protein and nucleic acid structure, a common theme among the research subjects are macromolecular assemblies and complex interacting systems. Other aspects of the work are directed in basic science research on the structure of retroviral proteins and host cellular factors involved in HIV expression. Work on the bacterial CLP P complex, part of a larger ATP-dependent protease complex, has resulted in a better crystal form containing only one 14-mer in the crystallographic asymmetric unit which diffracts to higher resolution. Crystallization studies of human histidyl tRNA synthetase, an autoantigen implicated in polymyositis, has resulted in two new crystal forms. Neither diffracts to high resolution and both contain many copies of the 50 kD protein subunit per crystallographic asymmetric unit. More progress has been made in our studies of the DNA """"""""polymerasome"""""""" from T4 phage. We have determined and refined the structures of three forms of the 5'->3' exonuclease (""""""""RNase H""""""""). The protein has structural features in common with a variety of nuclease and recombinases, but possesses a unique, new folding topology. Crystallization efforts are continuing on other members of this system including the polymerase and helicase. Two crystal forms and native and heavy-atom derivative data sets have been obtained for the small GP 59 helicase assembly factor. Our retroviral work has focused in two areas. Several forms of retroviral integrases have been expressed, purified and tested for crystallization. And several members of the host cell NFkB family, including p65-rel, I kappa-B and BCL-3 have likewise been expressed, purified and tested for feasibility in crystallization.
| Mueser, T C; Jones, C E; Nossal, N G et al. (2000) Bacteriophage T4 gene 59 helicase assembly protein binds replication fork DNA. The 1.45 A resolution crystal structure reveals a novel alpha-helical two-domain fold. J Mol Biol 296:597-612 |
